Get your patient on Zegalogue (Dasiglucagon)

ZEGALOGUE autoinjector and prefilled syringe are for subcutaneous injection only.

Instruct patients and their caregivers on the signs and symptoms of severe hypoglycemia. Because severe hypoglycemia requires the help of others to recover, instruct the patient to inform those around them about ZEGALOGUE and its Instructions For Use. Administer ZEGALOGUE as soon as possible when severe hypoglycemia is recognized.

Instruct the patient or caregiver to read the Instructions For Use at the time they receive a prescription for ZEGALOGUE. Emphasize the following instructions to the patient or caregiver:

• Administer ZEGALOGUE according to the printed instructions on the protective case label and the Instructions For Use.
• Visually inspect ZEGALOGUE prior to administration. The solution should appear clear, colorless, and free from particles. If the solution is discolored or contains particulate matter, do not use.
• Administer the injection in the lower abdomen, buttocks, thigh, or outer upper arm.
• Call for emergency assistance immediately after administering the dose.
• If there has been no response after 15 minutes, an additional dose of ZEGALOGUE may be administered while waiting for emergency assistance.
• When the patient has responded to treatment, give oral carbohydrates to restore liver glycogen and prevent recurrence of hypoglycemia.
• Do not attempt to reuse ZEGALOGUE. Each ZEGALOGUE device contains a single dose of dasiglucagon and cannot be reused.

The recommended dose of ZEGALOGUE in adults and pediatric patients aged 6 years and older is 0.6 mg administered by subcutaneous injection into the lower abdomen, buttocks, thigh, or outer upper arm.

If there has been no response after 15 minutes, an additional 0.6 mg dose of ZEGALOGUE from a new device may be administered.

The safety and effectiveness of ZEGALOGUE for the treatment of severe hypoglycemia in patients with diabetes have been established in pediatric patients aged 6 years and above. Use of ZEGALOGUE for this indication is supported by evidence from a study in 42 pediatric patients with type 1 diabetes [see Clinical Studies (14.2) ] .

The safety and effectiveness of ZEGALOGUE have not been established in pediatric patients younger than 6 years of age.

Clinical studies of ZEGALOGUE included too few patients 65 years of age and older to determine whether these patients respond differently from younger adult patients.

ZEGALOGUE is contraindicated in patients with pheochromocytoma because glucagon products may stimulate the release of catecholamines from the tumor [see Contraindications (4) ] . If the patient develops a substantial increase in blood pressure and a previously undiagnosed pheochromocytoma is suspected, 5 to 10 mg of phentolamine mesylate, administered intravenously, has been shown to be effective in lowering blood pressure.

In patients with insulinoma, administration of glucagon products may produce an initial increase in blood glucose; however, ZEGALOGUE administration may directly or indirectly (through an initial rise in blood glucose) stimulate exaggerated insulin release from an insulinoma and cause hypoglycemia. ZEGALOGUE is contraindicated in patients with insulinoma [see Contraindications (4) ] . If a patient develops symptoms of hypoglycemia after a dose of ZEGALOGUE, give glucose orally or intravenously.

Allergic reactions have been reported with glucagon products; these include generalized rash, and in some cases anaphylactic shock with breathing difficulties and hypotension. Advise patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions.

ZEGALOGUE is effective in treating hypoglycemia only if sufficient hepatic glycogen is present. Patients in states of starvation, with adrenal insufficiency or chronic hypoglycemia may not have adequate levels of hepatic glycogen for ZEGALOGUE administration to be effective. Patients with these conditions should be treated with glucose.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of ZEGALOGUE cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In clinical trials, 316 adult patients with type 1 diabetes and 20 pediatric patients with type 1 diabetes were exposed to ZEGALOGUE.

The data in Table 1 reflect exposure of 116 adult patients to ZEGALOGUE in 2 placebo-controlled trials (mean age 40 years). Table 2 reflects exposure of 20 pediatric patients exposed to ZEGALOGUE in a placebo-controlled trial. Eight patients were 7 to 11 years old, and 12 were 12 to 17 years old [see Clinical Studies (14) ] .

As with all therapeutic peptides, there is a potential for immunogenicity with ZEGALOGUE. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to ZEGALOGUE with the incidence of antibodies to other products may be misleading.

In clinical trials, 4/498 (<1%) of ZEGALOGUE-treated patients developed treatment-emergent anti-drug antibodies (ADAs). Two patients receiving a single dose of ZEGALOGUE had detectable ADAs to dasiglucagon for at least 14 months after dosing. One ADA-positive patient receiving multiple doses of ZEGALOGUE had ADAs with transient neutralizing activity and with cross-reactivity against native glucagon. Although no safety or efficacy concerns were noted for these ADA-positive subjects, it is unknown whether ADAs may affect pharmacokinetics, pharmacodynamics, safety, and/or effectiveness of the drug [see Clinical Studies (14) ] .

Dasiglucagon is a glucagon receptor agonist, which increases blood glucose concentration by activating hepatic glucagon receptors, thereby stimulating glycogen breakdown and release of glucose from the liver. Hepatic stores of glycogen are necessary for dasiglucagon to produce an antihypoglycemic effect.

After administration of ZEGALOGUE in adult patients with type 1 diabetes, the mean glucose increase from baseline at 90 minutes was 168 mg/dL (Figure 1).

Figure 1 Mean plasma glucose over time in adults with type 1 diabetes administered 0.6 mg dasiglucagon

In pediatric patients (7 to 17 years) with type 1 diabetes, the mean glucose increase at 60 minutes after administration of ZEGALOGUE was 162 mg/dL (Figure 2).

Figure 2 Mean plasma glucose over time in pediatric patients with type 1 diabetes administered 0.6 mg dasiglucagon

Trial A, NCT03378635: A total of 170 patients were randomized 2:1:1 to ZEGALOGUE, placebo, and glucagon for injection, stratified by injection sites (abdominal region, buttocks, thigh). The mean age of the patients was 39.1 years (96% were < 65 years), and the mean duration of diabetes was 20.0 years; 63% were male; 92% were White. The mean baseline plasma glucose was 58.8 mg/dL. The median time to plasma glucose recovery was statistically significantly shorter for ZEGALOGUE (10 minutes) versus placebo (40 minutes) (Table 4). Figure 3 shows the cumulative proportions of patients achieving plasma glucose recovery over time. The median time to plasma glucose recovery was numerically similar between ZEGALOGUE (10 minutes) and glucagon for injection (12 minutes).

Trial B, NCT03688711: A total of 45 patients were randomized 3:1 to ZEGALOGUE and placebo stratified by injection sites (buttocks, deltoid). The mean age of the patients was 41.0 years (95% were < 65 years), and the mean duration of diabetes was 22.5 years; 57% were male; 93% were White. The mean baseline plasma glucose was 55.0 mg/dL. The median time to plasma glucose recovery was statistically significantly shorter for ZEGALOGUE (10 minutes) versus placebo (35 minutes) (Table 4).

Figure 3 Time to plasma glucose recovery in Trial A

Trial C, NCT03667053: Pediatric patients aged 6 to 17 years and weighing ≥20 kg, were randomized 2:1:1 to ZEGALOGUE, placebo, and glucagon for injection, stratified by injection sites (abdominal region, thigh) and age groups (6-11 years and 12-17 years). A total of 42 patients were randomized. The mean age was 12.5 years (range 7 to 17 years), and the mean duration of diabetes was 5.9 years; 56% were male; 95% were White. The mean baseline plasma glucose was 72.0 mg/dL. The median time to plasma glucose recovery was statistically significantly shorter for ZEGALOGUE (10 minutes) versus placebo (30 minutes) (Table 5). Figure 4 shows the cumulative proportions of pediatric patients achieving plasma glucose recovery over time. The median time to plasma glucose recovery was numerically similar between ZEGALOGUE (10 minutes) and glucagon for injection (10 minutes).

Figure 4 Time to plasma glucose recovery in Trial C

ZEGALOGUE injection is a clear, colorless solution supplied as follows:

Store ZEGALOGUE in a refrigerator, 2°C to 8°C (36°F to 46°F). Keep away from the cooling element. Do not freeze.

ZEGALOGUE can be kept at room temperature between 20°C to 25°C (68°F to 77°F) for up to 12 months. Record the date when the product was removed from the refrigerator in the space provided on the protective case. Do not return the product to the refrigerator after storing at room temperature. Store in the provided protective case and protect from light.

Discard ZEGALOGUE after the end of the 12-month period at room temperature storage, or after the expiration date stated on the product, whichever occurs first.

The inside of the gray cap on ZEGALOGUE autoinjector contains dry natural rubber (a derivative of latex).

The inside of the gray needle cover on ZEGALOGUE prefilled syringe contains dry natural rubber (a derivative of latex).